The bisphosphonate 2-PEBP inhibits cyclosporin A induced high-turnover osteopenia in the rat.
A bisphosphonate, 2-PEBP (2-(2-pyridinyl) ethylidene bisphosphonate), was administered to animals receiving cyclosporin A (CsA) in an attempt to modify the high-turnover osteopenia associated with CsA therapy. Four groups of female Sprague-Dawley rats were administered either vehicle or CsA (15 mg/kg per day) by gavage for 28 days, together with either normal saline solution or 2-PEBP (1.72 mg/kg per day) given by intraperitoneal injection on days 0,1, and 2. The groups thus comprised Group A, vehicle/normal saline; group B, vehicle/2-PEBP; group C, CsA/normal saline solution; group D, CsA/2-PEBP. All rats received tetracycline hydrochloride by intraperitoneal injection for histomorphometric labeling. Blood was sampled on days 0, 7, 14, 21, and 28 for ionized calcium, serum phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D), blood urea nitrogen (BUN), creatinine, magnesium, and bone gla protein (BGP). Rats were killed on day 28 for tibial bone histomorphometry. All results were compared with group A. There were no significant differences in weight, ionized calcium, PTH, and serum phosphate between groups. Weight increased significantly by day 28 in all groups. Groups C and D revealed significantly higher levels of 1,25(OH)2D, BUN, and creatinine on days 14 and 28. Magnesium was significantly lower in groups C and D on days 14 and 28. BGP increased significantly in group C and decreased significantly in group B during the study. Tibial bone histomorphometry revealed high-turnover osteopenia in group C, significant improvement in both bone formation and resorption parameters in group D and hyperostosis in group B. Serum BGP reflected the histomorphometric indices of bone formation in each group.(ABSTRACT TRUNCATED AT 250 WORDS)
Movsowitz
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Division of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, PA 19141.
Epstein
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Fallon
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Ismail
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Thomas
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D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003524:Cyclosporins / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D008274:Magnesium / Q000097:blood; D008903:Minerals / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013977:Tibia / Q000166:cytology / Q000378:metabolism
D003524:Cyclosporins; D004164:Diphosphonates; D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D015675:Osteocalcin; C054229:2-(2-pyridyl)ethylidine-1,1-bisphosphonate; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium